Chen ZW, Kou Z, Halloran M, Simon M, Lee-Parritz D, Shen L, Fultz PN, Letvin NL; Beth Israel Hospital, Boston, MA.
The SIV/macaque model was employed to determine whether superantigen-mediated activation of the immune system, which may occur as a result of certain superimposed bacterial or viral infections in HIV-infected humans, can play a role in the immunopathogenesis of AIDS. Five uninfected rhesus monkeys inoculated with a defined superantigen, staphylococcal enterotoxin B (SEB) showed a transient expansion of both CD4+ and CD8+ T cells expressing members of TCR Vbeta3, 14, 15, 18, and 19 gene families. Eight similarly inoculated SIV mac-infected monkeys, however, exhibited a strikingly different response to the SEB superantigen. Their CD8+ cells expressing members of those Vbeta gene families demonstrated prolonged expansion in PBL following SEB inoculation. In contrast, CD4+ cell subpopulations expressing those selected Vbeta gene families displayed either a subtle or no detectable expansion in PBL of four SIV mac-infected animals in response to SEB. Interestingly, TUNEL analyses revealed numerous apoptotic lymphocytes in lymphoid tissues obtained on day 1 post-SEB injection in the animals. Furthermore, three SIV mac-infected monkeys died 2, 5, and 9 weeks following the SEB injection. In fact, SEB-induced activation was associated with a transient increase in plasma viral RNA in those animals. These studies suggest that CD4+ T lymphocytes of SIV mac-infected monkeys may be predisposed to apoptosis and/or anergy in response to superantigens. Persistent infection of monkeys with SIV mac can also predispose them to exaggerated reactions of CD8+ lymphocytes to bacterial superantigens. Such a profound immune activation can result in changes in viral dynamics. Thus, bacterial superantigens may contribute to disease progression in AIDS virus-infected individuals.
Keywords: AEGIS, SIV, Superantigens, Macaca mulatta, Simian Acquired Immunodeficiency Syndrome, CD4-Positive T-Lymphocytes, Enterotoxins, CD8-Positive T-Lymphocytes, T-Lymphocytes, Antigens, CD8, Macaca, Antigens, CD4, HIV-1, Acquired Immunodeficiency Syndrome, RNA, Viral, enterotoxin B, staphylococcal, Staphylococcus enterotoxin B, Animal, Human, AIDS
